Get your patient on Clenpiq - Sodium Picosulfate, Magnesium Oxide, And Anhydrous Citric Acid liquid (Sodium Picosulfate, Magnesium Oxide, And Anhydrous Citric Acid)
Clenpiq - Sodium Picosulfate, Magnesium Oxide, And Anhydrous Citric Acid liquid prescribing information
INDICATIONS AND USAGE
CLENPIQ is indicated for cleansing of the colon as a preparation for colonoscopy in adults and pediatric patients 9 years of age and older.
DOSAGE AND ADMINISTRATION
Important Administration Instructions
- Correct fluid and electrolyte abnormalities before administration of CLENPIQ [see Warnings and Precautions (5.1) ] .
- CLENPIQ is ready to drink. It is a clear solution with possible presence of visible particles and it does not need to be diluted prior to administration. One bottle of CLENPIQ is equivalent to one dose.
- Two doses of CLENPIQ are required for a complete preparation for colonoscopy as a Split-Dose regimen.
- The Split-Dose method consists of two separate doses: the first dose during the evening before the colonoscopy and the second dose the next day, during the morning prior to the colonoscopy [see Dosage and Administration (2.2) ] .
- Consume five or more 8-ounce cups of clear liquids after the first dose and four or more 8-ounce cups of clear liquids after the second dose [see Dosage and Administration (2.2) ] .
- Consume a variety of clear liquids. Clear liquids should include balanced electrolyte solution [see Warnings and Precautions (5.1 , 5.5) ] . Additional clear liquids, other than water, include black coffee or tea, plain jello, clear broth or bouillon, clear juices without pulp, ginger ale and other sodas, and frozen juice bars. Do not drink anything colored red or purple.
- Consume only clear liquids (no solid food) on the day before colonoscopy and until after the colonoscopy.
- Do not eat solid food or dairy and do not drink anything colored red or purple.
- Do not drink alcohol.
- Stop consumption of all liquids at least 2 hours before the colonoscopy.
- Do not take other laxatives while taking CLENPIQ.
- Administer oral medications at least one hour before starting each dose of CLENPIQ.
- If taking tetracycline or fluoroquinolone antibiotics, iron, digoxin, chlorpromazine, or penicillamine, take these medications at least 2 hours before and not less than 6 hours after administration of CLENPIQ.
Split-Dose Dosage Regimen
The recommended dosage in adults and pediatric patients 9 years of age and older is shown below. Instruct patients to take two separate doses in conjunction with liquids, as follows:
Dose 1 – On the day before colonoscopy:
- Instruct patients to consume only clear liquids (no solid food or dairy) on the day before the colonoscopy up until 2 hours before the time of the colonoscopy.
- Take the first dose (1 bottle) of CLENPIQ during the evening before the colonoscopy (e.g., 5:00 PM to 9:00 PM).
- Consume at least five 8-ounce cups (cup provided) of clear liquids after the CLENPIQ dose over the next 5 hours.
- If severe bloating, distention, or abdominal pain occurs, following the first dose, delay the second dose until the symptoms resolve.
Dose 2 – Next morning on the day of colonoscopy (start approximately 5 hours prior to colonoscopy):
- Continue to consume only clear liquids (no solid food or dairy).
- Take the second dose (the second bottle) of CLENPIQ.
- Consume four or more 8-ounce cups (cup provided) of clear liquids after the CLENPIQ dose and up to 2 hours before the colonoscopy.
DOSAGE FORMS AND STRENGTHS
Oral solution: Each bottle contains 10 mg of sodium picosulfate, 3.5 grams of magnesium oxide, and 12 grams of anhydrous citric acid in 175 mL of colorless to slightly yellow, clear solution with possible presence of visible particles.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
There are no data with CLENPIQ use in pregnant women to determine a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, no adverse developmental effects were observed in pregnant rats when sodium picosulfate, magnesium oxide, and anhydrous citric acid were administered orally at doses 1.2 times the recommended human dose based on body surface area during organogenesis.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Animal Data
Reproduction studies with sodium picosulfate, magnesium oxide, and anhydrous citric acid have been performed in pregnant rats following oral administration of up to 2000 mg/kg twice daily (about 1.2 times the recommended human dose based on body surface area) during the period of organogenesis. There was no evidence of harm to the fetus due to sodium picosulfate, magnesium oxide, and anhydrous citric acid. The reproduction study in rabbits was not adequate, as treatment-related mortalities were observed at all doses. A pre and postnatal development study with sodium picosulfate, magnesium oxide, and anhydrous citric acid in rats showed no evidence of any adverse effect on pre and postnatal development at oral doses up to 2000 mg/kg twice daily (about 1.2 times the recommended human dose based on body surface area).
Published reproduction studies with sodium picosulfate in pregnant rats and rabbits during the period of organogenesis did not show evidence of harm to the fetus at doses up to 100 mg/kg (approximately 49 and 98 times, respectively, the recommended human dose of 10 mg sodium picosulfate based on body surface area).
Lactation
Risk Summary
There are no data on the presence of magnesium oxide or anhydrous citric acid in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Published data on lactating women indicate that the active metabolite of sodium picosulfate, bis-( p -hydroxyphenyl)-pyridyl-2-methane (BHPM) remained below the limit of detection (1 ng/mL) in breast milk after both single and multiple doses of 10 mg/day. There are no data on the effects of sodium picosulfate on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for CLENPIQ and any potential adverse effects on the breastfed infant from CLENPIQ or the underlying maternal condition.
Pediatric Use
The safety and effectiveness of CLENPIQ have been established for cleansing of the colon as a preparation for colonoscopy in pediatric patients 9 years of age and older. Use of CLENPIQ in this age group is supported by evidence from adequate and well-controlled trials in adults and a single, dose-ranging, controlled trial in 78 pediatric patients 9 to 16 years of age all of which evaluated another oral product of sodium picosulfate, magnesium oxide, and anhydrous citric acid [see Clinical Studies (14) ]. The safety profile in this pediatric population was similar to that seen in adults [see Adverse Reactions (6.1) ] . Monitor for possible hypoglycemia in pediatric patients, as CLENPIQ has no caloric substrate.
The safety and effectiveness of CLENPIQ in pediatric patients less than 9 years of age have not been established.
Geriatric Use
Of the 448 adult patients in Study 1 who received CLENPIQ, 124 (28%) patients were 65 years of age or older. No overall differences in safety or effectiveness were observed between geriatric patients and younger patients, and other reported clinical experience has not identified differences in responses between elderly and younger patients. Elderly patients are more likely to have decreased hepatic, renal, or cardiac function and may be more susceptible to adverse reactions resulting from fluid and electrolyte abnormalities [see Warnings and Precautions (5.1) ].
Renal Impairment
CLENPIQ is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min), as accumulation of magnesium in plasma may occur [see Contraindications (4) ] . Patients with less severe renal impairment or patients taking concomitant medications that may affect renal function may be at increased risk for renal injury [see Warnings and Precautions (5.3) ] . Advise these patients of the importance of adequate hydration before, during, and after the use of CLENPIQ [see Dosage and Administration (2.1) ] . Consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients.
CONTRAINDICATIONS
CLENPIQ is contraindicated in the following conditions:
- Patients with severe renal impairment (creatinine clearance less than 30 mL/minute), which may result in accumulation of magnesium [see Warnings and Precautions (5.3) ].
- Gastrointestinal obstruction or ileus [see Warnings and Precautions (5.6) ].
- Bowel perforation [see Warnings and Precautions (5.6) ].
- Toxic colitis or toxic megacolon.
- Gastric retention.
- Hypersensitivity to any of the ingredients in CLENPIQ [see Adverse Reactions (6.2) ].
WARNINGS AND PRECAUTIONS
Serious Fluid and Electrolyte Abnormalities
Advise patients to hydrate adequately before, during, and after the use of CLENPIQ. Use caution in patients with congestive heart failure when replacing fluids. If a patient develops significant vomiting or signs of dehydration including signs of orthostatic hypotension after taking CLENPIQ, consider performing post-colonoscopy lab tests (electrolytes, creatinine, and BUN) and treat accordingly. Approximately 20% of patients in both arms (sodium picosulfate, magnesium oxide, and anhydrous citric acid, or 2 L of PEG + E plus two × 5-mg bisacodyl tablets) of clinical trials of another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product had orthostatic changes in blood pressure and/or heart rate on the day of colonoscopy and up to seven days post colonoscopy. In a single study of patients 9 to 16 years of age, approximately 20% of patients who received another oral product of sodium picosulfate, magnesium oxide, and anhydrous citric acid had orthostatic changes (changes in blood pressure and/or heart rate) compared with approximately 7% of those who received the comparator (PEG) [see Clinical Studies (14) ] . These changes occurred up to five days post colonoscopy.
Fluid and electrolyte disturbances can lead to serious adverse reactions including cardiac arrhythmias, seizures, renal impairment, and syncope [see Warnings and Precautions (5.5) ] . Correct fluid and electrolyte abnormalities before treatment with CLENPIQ. Advise patients to consume a variety of clear liquids (e.g., balanced electrolyte solution), and not only water after each dose of CLENPIQ. In addition, use caution when prescribing CLENPIQ for patients who have conditions or who are using medications that increase the risk for fluid and electrolyte disturbances or that may increase the risk of seizure, arrhythmia, and renal impairment [see Drug Interactions (7.1) ] .
Seizures
There have been reports of generalized tonic-clonic seizures and/or loss of consciousness with the use of bowel preparation products in patients with no prior history of seizures. The seizure cases were associated with electrolyte abnormalities (e.g., hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia) and low serum osmolality. The neurologic abnormalities resolved with correction of fluid and electrolyte abnormalities.
Use caution when prescribing CLENPIQ for patients with a history of seizures and in patients at risk of seizure, such as patients taking medications that lower the seizure threshold (e.g., tricyclic antidepressants), patients withdrawing from alcohol or benzodiazepines, patients with known or suspected hyponatremia [see Adverse Reactions (6.2) ] .
Use in Patients with Renal Impairment
CLENPIQ is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min), accumulation of magnesium in plasma may occur. Use caution when prescribing CLENPIQ for patients with mild to moderate renal impairment or patients taking concomitant medications that may affect renal function (such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or non-steroidal anti-inflammatory drugs) [see Drug Interactions (7.1) ] . These patients may be at increased risk for renal injury. Advise these patients of the importance of adequate hydration before, during, and after the use of CLENPIQ. Consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients.
Cardiac Arrhythmias
There have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. Use caution when prescribing CLENPIQ for patients at increased risk of arrhythmias (e.g., patients with a history of prolonged QT, uncontrolled arrhythmias, recent myocardial infarction, unstable angina, congestive heart failure, or cardiomyopathy). Consider pre-dose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.
Syncope
Syncope has been reported with CLENPIQ in the postmarketing setting. Some cases were serious events that included falls with associated head injuries or fractures requiring hospitalization. In some cases, electrolyte abnormalities were also present (e.g., hyponatremia and hypokalemia). Cases have been reported after one or two CLENPIQ doses and many of these cases occurred within 12 hours of dosing. Patients should be aware of the risk of syncope during treatment and adequately hydrate before, during, and after the use of CLENPIQ. Advise patients to consume a variety of clear liquids (e.g., balanced electrolyte solution), not only water after each dose of CLENPIQ and to get up gradually from a lying or sitting position [see Warnings and Precautions (5.1) ] .
Colonic Mucosal Ulceration, Ischemic Colitis, and Ulcerative Colitis
Osmotic laxatives may produce colonic mucosal aphthous ulcerations and there have been reports of more serious cases of ischemic colitis requiring hospitalization. Concurrent use of additional stimulant laxatives with CLENPIQ may increase this risk. Consider the potential for mucosal ulcerations when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease [see Adverse Reactions (6.2) ] .
Use in Patients with Significant Gastrointestinal Disease
If gastrointestinal obstruction or perforation is suspected, perform appropriate diagnostic studies to rule out these conditions before administering CLENPIQ [see Contraindications (4) ] . Use with caution in patients with severe active ulcerative colitis.
Aspiration
Patients with impaired gag reflex are at risk for regurgitation or aspiration during the administration of CLENPIQ. Observe these patients during the administration of CLENPIQ.
ADVERSE REACTIONS
The following serious or otherwise important adverse reactions for bowel preparations are described elsewhere in the labeling:
- Serious Fluid and Electrolyte Abnormalities [see Warnings and Precautions (5.1) ]
- Seizures [see Warnings and Precautions (5.2) ]
- Use in Patients with Renal Impairment [see Warnings and Precautions (5.3) ]
- Cardiac Arrhythmias [see Warnings and Precautions (5.4) ]
- Syncope [see Warnings and Precautions (5.5) ]
- Colonic Mucosal Ulceration, Ischemic Colitis and Ulcerative Colitis [see Warnings and Precautions (5.6) ]
- Use in Patients with Significant Gastrointestinal Disease [see Warnings and Precautions (5.7) ]
- Aspiration [see Warnings and Precautions (5.8) ]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.
Adults
Clinical Study of CLENPIQ - Study 1
Table 1 displays the most common adverse reactions in a randomized, multicenter, assessor-blinded, non-inferiority trial of CLENPIQ for colon cleansing in adults (Study 1). CLENPIQ was compared to another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product, both administered according to the Split-Dose dosage regimen [see Clinical Studies (14) ] .
| Adverse Reaction | Split-Dose Regimen | |
|---|---|---|
| CLENPIQ (N=448) % | Sodium picosulfate, magnesium oxide, and anhydrous citric acid Powder for reconstitution (N=453) % | |
| Nausea | 3 | 3 |
| Headache | 3 | 3 |
| Hypermagnesemia Magnesium levels returned to normal within one week after colonoscopy in all patients in the CLENPIQ group. | 2 | 5 |
| Abdominal pain Abdominal pain included reports of abdominal pain, abdominal pain upper, and abdominal pain lower. | 2 | 2 |
| Dehydration or dizziness | 2 | 2 |
Clinical Study of Another Sodium Picosulfate, Magnesium Oxide and Anhydrous Citric Acid Product - Study 2
In a randomized, multicenter, investigator-blinded, active-controlled clinical trial for colon cleansing in adults, another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product was compared with a regimen of two liters (2 L) of polyethylene glycol plus electrolytes solution (PEG + E) and two 5-mg bisacodyl tablets (Study 2). In this study the protocol specified that abdominal bloating, distention, pain/cramping, and watery diarrhea, which are known to occur in response to bowel preparation, were documented as adverse events only if they required medical intervention (such as a change in study drug or led to discontinuation, therapeutic or diagnostic procedures, met the criteria for serious adverse event) or showed clinically significant worsening during the study that was not in the frame of the usual clinical course, as determined by the investigator. The most common adverse reactions in Study 2 are shown in Table 2.
| Adverse Reaction | Split-Dose Regimen | |
|---|---|---|
| Sodium picosulfate, magnesium oxide, and anhydrous citric acid (N=305) % | 2 L PEG + E 2 L PEG + E = two liters polyethylene glycol plus electrolytes solution with 2 × 5-mg bisacodyl tablets (N=298) % | |
| Nausea | 3 | 4 |
| Headache | 2 | 2 |
| Vomiting | 1 | 3 |
Electrolyte Abnormalities
In Study 1, rates of abnormal electrolyte shifts were generally similar between CLENPIQ and another sodium picosulfate, magnesium oxide, and anhydrous citric acid product (Table 3). In general, these shifts were transient and not clinically significant.
In Study 2, sodium picosulfate, magnesium oxide, and anhydrous citric acid was in general associated with numerically higher rates of abnormal electrolyte shifts on the day of colonoscopy compared to the control regimen (Table 3). These shifts were transient in nature and numerically similar between treatment arms at the Day 28 visit.
| Laboratory Parameter (direction of change) | Visit | Split-Dose Regimen Study 1 | Split-Dose Regimen Study 2 | ||
|---|---|---|---|---|---|
| CLENPIQ | Sodium picosulfate, magnesium oxide, and anhydrous citric acid Powder for reconstitution | Sodium picosulfate, magnesium oxide, and anhydrous citric acid | 2 L PEG+E with 2 × 5 mg bisacodyl tablets | ||
| n/N (%) | n/N (%) | ||||
| N/A: not applicable. | |||||
| Potassium (low) | Day of Colonoscopy | 34/422 (8.1) | 10/423 (2.4) | 19/260 (7.3) | 11/268 (4.1) |
| 24-48 hours | 13/417 (3.1) | 3/423 (0.7) | 3/302 (1.0) | 2/294 (0.7) | |
| Day 7 | 7/420 (1.7) | 6/425 (1.4) | 11/285 (3.9) | 8/279 (2.9) | |
| Day 28 | 3/421 (0.7) | 7/423 (1.7) | 11/284 (3.9) | 8/278 (2.9) | |
| Sodium (low) | Day of Colonoscopy | 4/426 (0.9) | 23/443 (5.2) | 11/298 (3.7) | 3/295 (1.0) |
| 24-48 hours | 6/423 (1.4) | 9/441 (2.0) | 1/303 (0.3) | 1/295 (0.3) | |
| Day 7 | 6/423 (1.4) | 9/440 (2.0) | 2/300 (0.7) | 1/292 (0.3) | |
| Day 28 | 8/427 (1.9) | 9/439 (2.1) | 2/299 (0.7) | 3/291 (1.0) | |
| Chloride (low) | Day of Colonoscopy | 23/437 (5.3) | 16/444 (3.6) | 11/301 (3.7) | 1/298 (0.3) |
| 24-48 hours | 3/434 (0.7) | 3/442 (0.7) | 1/303 (0.3) | 0/295 (0.0) | |
| Day 7 | 3/434 (0.7) | 2/441 (0.5) | 1/303 (0.3) | 3/295 (1.0) | |
| Day 28 | 4/438 (0.9) | 1/440 (0.2) | 2/302 (0.7) | 3/294 (1.0) | |
| Magnesium (high) | Day of Colonoscopy | 112/431 (26.0) | 143/440 (32.5) | 34/294 (11.6) | 0/294 (0.0) |
| 24-48 hours | 23/427 (5.4) | 21/440 (4.8) | 0/303 (0.0) | 0/295 (0.0) | |
| Day 7 | 11/428 (2.6) | 9/440 (2.0) | 0/297 (0.0) | 1/291 (0.3) | |
| Day 28 | 10/432 (2.3) | 12/438 (2.7) | 1/296 (0.3) | 2/290 (0.7) | |
| Calcium (low) | Day of Colonoscopy | 8/436 (1.8) | 1/446 (0.2) | 2/292 (0.7) | 1/286 (0.3) |
| 24-48 hours | 1/434 (0.2) | 0/444 (0.0) | 0/303 (0.0) | 0/295 (0.0) | |
| Day 7 | 0/434 (0.0) | 0/444 (0.0) | 0/293 (0.0) | 1/283 (0.4) | |
| Day 28 | 0/439 (0.0) | 2/442 (0.5) | 0/292 (0.0) | 1/282 (0.4) | |
| Bicarbonate (low) | Day of Colonoscopy | 6/431 (1.4) | 35/438 (8.0) | N/A Bicarbonate was not analyzed in Study 2. | N/A |
| 24-48 hours | 40/430 (9.3) | 43/434 (9.9) | N/A | N/A | |
| Day 7 | 37/430 (8.6) | 40/438 (9.1) | N/A | N/A | |
| Day 28 | 33/433 (7.6) | 43/436 (9.9) | N/A | N/A | |
| Creatinine (high) | Day of Colonoscopy | 6/427 (1.4) | 1/432 (0.2) | 5/260 (1.9) | 13/268 (4.9) |
| 24-48 hours | 6/425 (1.4) | 5/431 (1.2) | 1/303 (0.3) | 0/295 (0.0) | |
| Day 7 | 5/426 (1.2) | 4/431 (0.9) | 10/264 (0.4) | 13/267 (4.8) | |
| Day 28 | 4/429 (0.9) | 6/429 (1.4) | 11/264 (4.2) | 14/265(5.3) | |
Pediatrics
In the pediatric patients aged 9 to 16 years who received another oral product of sodium picosulfate, magnesium oxide, and anhydrous citric acid, the most common adverse reactions (> 5%) were nausea, vomiting, and abdominal pain [see Clinical Studies (14) ] . Electrolytes abnormalities were observed in pediatric patients similar to those seen in adults. Three patients had abnormally low glucose levels (40 to 47 mg/dL). Two patients received sodium picosulfate, magnesium oxide, and anhydrous citric acid and one received the comparator (PEG). The abnormal values occurred at the colonoscopy visit for one patient (sodium picosulfate, magnesium oxide, and anhydrous citric acid) and at the 5-day follow up visit for the other two patients (sodium picosulfate, magnesium oxide, and anhydrous citric acid and PEG). All three patients were asymptomatic.
Postmarketing Experience
The following adverse reactions have been identified during post approval use of oral sodium picosulfate, magnesium oxide, and anhydrous citric acid products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hypersensitivity : rash, urticaria, and purpura
Gastrointestinal: abdominal pain, diarrhea, fecal incontinence, proctalgia, vomiting, reversible aphthoid ileal ulcers, and ischemic colitis [see Warnings and Precautions (5.5) ]
Neurologic: generalized tonic-clonic seizures with and without hyponatremia in epileptic patients, and syncope [see Warnings and Precautions (5.2 , 5.5) ] .
DRUG INTERACTIONS
Drugs That May Increase Risks of Fluid and Electrolyte Abnormalities
Use caution when prescribing CLENPIQ for patients with conditions or who are taking other drugs, that increase the risk for fluid and electrolyte disturbances or may increase the risk of renal impairment, seizures, syncope, arrhythmias or QT prolongation in the setting of fluid and electrolyte abnormalities [see Warnings and Precautions (5.1 , 5.2 , 5.3 , 5.4 , 5.5) ] .
Potential for Reduced Drug Absorption
CLENPIQ can reduce the absorption of other co-administered drugs [see Dosage and Administration (2.1) ] :
- Administer oral medications at least one hour before of the start of administration of CLENPIQ.
- Administer tetracycline and fluoroquinolone antibiotics [see Drug Interactions (7.3) ] , iron, digoxin, chlorpromazine, and penicillamine at least 2 hours before and not less than 6 hours after administration of CLENPIQ to avoid chelation with magnesium.
Antibiotics
Prior or concomitant use of antibiotics with CLENPIQ may reduce efficacy of CLENPIQ as conversion of sodium picosulfate to its active metabolite BHPM is mediated by colonic bacteria.
DESCRIPTION
CLENPIQ (sodium picosulfate, magnesium oxide, and anhydrous citric acid) oral solution is a stimulant and osmotic laxative that is provided as a cranberry-flavored, colorless to slightly yellow, clear solution with possible presence of visible particles. CLENPIQ is supplied as two bottles in each carton.
Each bottle of CLENPIQ contains 10 mg sodium picosulfate, USP; 3.5 g magnesium oxide, USP; and 12 g anhydrous citric acid, USP. The product also contains the following inactive ingredients:
acesulfame potassium, cranberry flavor, disodium edetate, malic acid, sodium benzoate, sodium hydroxide, sodium metabisulfite, sucralose, and water. The cranberry flavor contains glyceryl triacetate (triacetin), maltodextrin, and sodium octenyl succinated starch.
The following is a description of the three active ingredients contained in CLENPIQ:
Sodium picosulfate is a stimulant laxative.
Sodium Picosulfate
- Chemical name: 4,4´-(2-pyridylmethylene) diphenyl bis(hydrogen sulfate) disodium salt, monohydrate
- Chemical formula: C 18 H 13 NNa 2 O 8 S 2 ∙H 2 O
- Molecular weight: 499.4
- Structural formula:
Sodium picosulfate
Magnesium citrate, which is formed in solution by the combination of magnesium oxide and anhydrous citric acid, is an osmotic laxative.
Magnesium Oxide
- Chemical name: Magnesium oxide
- Chemical formula: Mg O
- Molecular weight: 40.3
- Structural formula: Mg O
Anhydrous Citric Acid
- Chemical name: 2-hydroxypropane-1,2,3-tricarboxylic acid
- Chemical formula: C 6 H 8 O 7
- Molecular weight: 192.1
- Structural formula:
Anhydrous citric acid
CLINICAL PHARMACOLOGY
Mechanism of Action
Sodium picosulfate is hydrolyzed by colonic bacteria to form an active metabolite: bis-(p-hydroxy-phenyl)-pyridyl-2-methane, BHPM, which acts directly on the colonic mucosa to stimulate colonic peristalsis. Magnesium oxide and citric acid react to create magnesium citrate in solution, which is an osmotic agent that causes water to be retained within the gastrointestinal tract.
Pharmacodynamics
The stimulant laxative activity of sodium picosulfate together with the osmotic laxative activity of magnesium citrate produces a purgative effect which, when ingested with additional liquids, produces watery diarrhea.
Pharmacokinetics
Absorption
After administration of the first dose of another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product in 16 healthy subjects, the mean ± SD maximum plasma concentration (C max ) for picosulfate of 2.3 ± 1.4 ng/mL was reached at 2 hours. After administration of two doses separated by 6 hours, the mean ± SD plasma C max for picosulfate of 3.2 ± 2.6 ng/mL was reached at approximately 7 hours after the first dose administration. In the same study, the uncorrected plasma magnesium concentration reached a C max of approximately 1.9 mEq/L at 10 hours after the first dose administration, which represents an approximately 20% increase from baseline.
In patients scheduled to have an elective colonoscopy who received the Split-Dose dosage regimen of CLENPIQ, the mean ± SD plasma concentration for picosulfate was 1.05 ± 0.83 ng/mL at 15 minutes pre-second dose, 2.98 ± 1.27 ng/mL at 1-2 hours post-second dose, and 1.81 ± 0.86 ng/mL at 3-6 hours post-second dose.
Metabolism and Elimination
Metabolism and Excretion
Plasma concentrations of the free BHPM were below the lower limit of quantification (0.1 ng/mL) in 13 out of 16 subjects studied. The fraction of the sodium picosulfate dose excreted unchanged in urine was 0.1%. In urine, the majority of excreted BHPM was in the glucuronide-conjugated form. The terminal half-life of sodium picosulfate was 7.4 hours.
Use in Specific Populations
Pediatric Patients
Pharmacokinetics of picosulfate was studied in pediatric patients aged from 9 to 16 years old. The half-life of picosulfate was 7 hours. The picosulfate reached the mean ± SD C max of 3.5 ± 2.1 ng/mL at approximately 6 to 7 hours. The baseline uncorrected mean serum magnesium concentration was 2.02 mEq/L at 10 hours after the first dose of sodium picosulfate, magnesium oxide, and anhydrous citric acid and ranged from 1.7 to 2.46 mEq/L.
Drug Interaction Studies
In an in vitro study using human liver microsomes, sodium picosulfate did not inhibit the major CYP enzymes (CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4/5) evaluated. Based on an in vitro study using freshly isolated hepatocyte culture, sodium picosulfate is not an inducer of CYP1A2, CYP2B6, or CYP3A4/5.
NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals to evaluate carcinogenic potential or studies to evaluate mutagenic potential have not been performed with CLENPIQ.
Sodium picosulfate was not mutagenic in the Ames test, the mouse lymphoma assay, and the mouse bone marrow micronucleus test.
In an oral fertility study in rats, sodium picosulfate, magnesium oxide, and anhydrous citric acid did not cause any significant adverse effect on male or female fertility parameters up to a maximum dose of 2000 mg/kg twice daily (about 1.2 times the recommended human dose based on body surface area).
CLINICAL STUDIES
Adults
Clinical Study with CLENPIQ – Study 1
The colon-cleansing efficacy of CLENPIQ was evaluated in a randomized, investigator-blinded, active-controlled, multicenter non-inferiority trial in the US and Canada in adult patients scheduled to have an elective colonoscopy (NCT03017235). Patients were randomized to CLENPIQ or another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product. Both products were administered by the "Split-Dose" (evening before and day of) dosing, where the first dose was taken the evening before the colonoscopy (between 5:00 and 9:00 PM), followed by at least five (5) 8-ounce glasses of clear liquid, and the second dose was taken the morning of the colonoscopy (at least 5 hours prior to but no more than 9 hours prior to colonoscopy), followed by at least four (4) 8-ounce glasses of clear liquid. Patients in both treatment groups were limited to a clear liquid diet on the day before the procedure (24 hours before).
A total of 901 adult patients were included in the primary efficacy analysis. Patients ranged in age from 20 to 80 years (mean age 57 years); 56% were female and 44% male. Self-identified race was approximately distributed as follows: 85% White, 10% Black, 2% Asian, and 3% other. Approximately 15% of patients self-identified their ethnicity as Hispanic or Latino.
The primary efficacy endpoint was the proportion of patients with successful overall colon cleansing, as assessed by blinded colonoscopists using the Modified Aronchick Scale. The Modified Aronchick Scale is a validated tool used to assess overall colon cleansing prior to suctioning or cleaning. Successful colon cleansing was defined as bowel preparations with >90% of the mucosa seen and mostly liquid stool that were graded excellent (minimal suctioning needed for adequate visualization) or good (significant suctioning needed for adequate visualization) by the colonoscopist.
In the trial, CLENPIQ was non-inferior and also met the pre-specified criteria for superiority to the comparator for overall colon cleansing. Efficacy results are provided in Table 4.
| CLENPIQ | Sodium picosulfate, magnesium oxide, and anhydrous citric acid Powder for reconstitution | Difference between treatment groups Difference and 95% CI are based on stratified difference in proportions, where the stratification weight is based on Cochran-Mantel-Haenszel weight. | |
|---|---|---|---|
| % (n/N) | % (n/N) | Difference | 95% CI |
| 87.7% (393/448) | 81.5% (369/453) | 6.3% | (1.8%, 10.9%) Non-inferior and superior to sodium picosulfate, magnesium oxide, and anhydrous citric acid |
Clinical Study of Another Oral Sodium Picosulfate, Magnesium Oxide and Anhydrous Citric Acid Product – Study 2
The colon cleansing efficacy of another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product was evaluated in a randomized, investigator-blinded, active-controlled, multicenter US non-inferiority trial in adult patients scheduled to have an elective colonoscopy (NCT01073930).
Patients were randomized to sodium picosulfate, magnesium oxide, and anhydrous citric acid group or polyethylene glycol plus electrolytes (PEG + E) and bisacodyl.
- Sodium picosulfate, magnesium oxide, and anhydrous citric acid was given by "Split-Dose" (evening before and day of) dosing, where the first dose was taken the evening before the colonoscopy (between 5:00 and 9:00 PM), followed by five (5) 8-ounce glasses of clear liquid, and the second dose was taken the morning of the colonoscopy (at least 5 hours prior to but no more than 9 hours prior to colonoscopy), followed by three (3) 8-ounce glasses of clear liquid.
- The comparator was given as two liters of polyethylene glycol plus electrolytes solution (PEG + E) and two 5-mg bisacodyl tablets, administered the day before the procedure.
All patients in both treatment groups were limited to a clear liquid diet on the day before the procedure (24 hours before).
A total of 601 adult patients were included in the primary efficacy analysis. Patients ranged in age from 18 to 80 years (mean age 55 years); 59% were female and 41% male. Self-identified race was distributed as follows: 88% White, 10% Black, and less than 2% other. Of these, 2% self-identified their ethnicity as Hispanic or Latino.
The primary efficacy endpoint was the proportion of patients with successful colon cleansing, as assessed by blinded colonoscopists using the Aronchick Scale. The Aronchick scale is a tool used to assess overall colon cleansing. Successful colon cleansing was defined as bowel preparations with >90% of the mucosa seen and mostly liquid stool that were graded excellent (minimal suctioning needed for adequate visualization) or good (significant suctioning needed for adequate visualization) by the colonoscopist.
Sodium picosulfate, magnesium oxide, and anhydrous citric acid was non-inferior to the comparator. In addition, sodium picosulfate, magnesium oxide, and anhydrous citric acid met the pre-specified criteria for superiority to the comparator for colon cleansing. Efficacy results are provided in Table 5.
| Sodium picosulfate, magnesium oxide, and anhydrous citric acid | 2 L PEG+E 2 L PEG + E = two liters polyethylene glycol plus electrolytes solution. with 2 × 5-mg bisacodyl tablets | Difference between treatment groups | |
|---|---|---|---|
| % (n/N) | % (n/N) | Difference | 95% CI |
| 84% (256/304) | 74% (221/297) | 10% | (3.4%, 16.2%) Non-inferior and superior to 2 L PEG+E with 2 × 5-mg bisacodyl tablets |
Pediatric Patients 9 Years of Age and Older
The safety and efficacy of CLENPIQ in pediatric patients 9 years of age and older has been established based on another oral product of sodium picosulfate, magnesium oxide and anhydrous citric acid provided in powder packets for reconstitution (NCT01928862).
Sodium picosulfate, magnesium oxide, and anhydrous citric acid was evaluated for colon cleansing in a randomized, assessor-blind, multicenter, dose-ranging, active-controlled study in 78 pediatric patients 9 years to 16 years of age. The majority of patients were female (68%), white (91%), and of non-Hispanic or non-Latino ethnicity (95%). The mean age was 12 years of age. All 78 patients were included in the primary efficacy analysis.
Patients aged 9 years to 12 years were randomized into 3 arms (1:1:1):
- Sodium picosulfate, magnesium oxide, and anhydrous citric acid one-half packet per dose administered as two doses
- Sodium picosulfate, magnesium oxide, and anhydrous citric acid one packet per dose administered as two doses
- Comparator (oral PEG-based solution per local standard of care).
Patients aged 13 years to 16 years were randomized into 2 arms (1:1):
- Sodium picosulfate, magnesium oxide, and anhydrous citric acid one packet per dose administered as two doses
- Comparator (oral PEG-based solution per local standard of care)
Patients randomized to sodium picosulfate, magnesium oxide, and anhydrous citric acid had two options for dosing, as determined by the investigator. The "Split-Dose" regimen was the preferred method and the "Day-Before" regimen was the alternative method if the "Split-Dose" was not appropriate.
"Split-Dose" Regimen: (evening before and day of) dosing, where the first dose was taken the evening before the colonoscopy (between 5:00 and 9:00 PM), followed by five (5) 8-ounce glasses of clear liquid, and the second dose was taken the morning of the colonoscopy (at least 5 hours prior to but no more than 9 hours prior to colonoscopy), followed by three (3) 8-ounce glasses of clear liquid.
"Day-Before" Regimen: (afternoon/evening before only) dosing, where both doses were taken separately on the day before the colonoscopy, with the first dose taken in the afternoon (between 4:00 and 6:00 PM), followed by five (5) 8-ounce glasses of clear liquid, and the second dose taken in the late evening (approximately 6 hours later, between 10:00 PM and 12:00 AM), followed by three (3) 8-ounce glasses of clear liquid.
All patients randomized to sodium picosulfate, magnesium oxide, and anhydrous citric acid was limited to a clear liquid diet on the day before the procedure. Those who received the comparator were given dietary instructions per the trial site's standard of care.
The primary efficacy endpoint was the proportion of patients with successful colon cleansing as defined as a rating of either "Excellent" (> 90% of mucosa seen, mostly liquid stool, minimal suctioning needed for adequate visualization) or "Good" (> 90% of mucosa seen, mostly liquid stool, significant suctioning needed for adequate visualization) using the Aronchick scale, as assessed by blinded colonoscopists.
The sodium picosulfate, magnesium oxide, and anhydrous citric acid regimen of one-half packet per dose administered as two doses did not demonstrate comparable efficacy to the comparator, PEG, in patients 9 to 12 years of age and is not a CLENPIQ recommended dosage regimen [see Dosage and Administration (2) ] .
The sodium picosulfate, magnesium oxide, and anhydrous citric acid regimen of one packet per dose administered as two doses demonstrated successful colon cleansing in both the 9 to 12 year age group and the 13 to 16 year age group. The efficacy rates were similar to those observed in the PEG groups, as shown in Table 6.
| Sodium Picosulfate, Magnesium Oxide, and Anhydrous Citric Acid, One Packet Administered as Two Doses either as Split Dose or Day Before Regimen Of the 32 patients, 9 received the Split Dose Regimen and 23 the Day Before Regimen | PEG Comparator Oral PEG-based preparation was used in the study as per standard of care | |||
|---|---|---|---|---|
| % (n/N) | 95% CI | % (n/N) | 95% CI | |
| Age 9-12 | 88% (14/16) | (62, 98) | 81% (13/16) | (54, 96) |
| Age 13-16 | 81% (13/16) | (54, 96) | 86% (12/14) | (57, 98) |
HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
CLENPIQ is supplied in a carton containing two bottles, each holding 175 mL of cranberry-flavored, colorless to slightly yellow, clear oral solution with possible presence of visible particles. Each bottle contains 10 mg sodium picosulfate, 3.5 g magnesium oxide, and 12 g anhydrous citric acid. An eight-ounce cup for measuring liquids for hydration is also supplied.
CLENPIQ Cranberry flavor: NDC# 55566-6800-1.
Storage
Store CLENPIQ at 25°C (77°F). Excursions permitted at 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature]. Do not refrigerate or freeze.
Instructions for Use CLENPIQ ® (CLEN-pik) (sodium picosulfate, magnesium oxide, and anhydrous citric acid) oral solution
| NOTE: Do not refrigerate or freeze CLENPIQ. CLENPIQ is ready to drink and does not need to be mixed with anything. CLENPIQ is a clear liquid that may have particles. |
READ BEFORE Taking CLENPIQ
If you have questions before you start CLENPIQ, talk to your healthcare provider.
Take CLENPIQ using the Split-Dose method. This means you will take 2 separate doses. Each bottle is 1 dose and has the same ingredients. You can drink either bottle first.
- Drink the first bottle the evening before your colonoscopy.
- Drink the second bottle the morning of your colonoscopy.
Start a clear-liquid diet the day before your colonoscopy. Do not eat any solid foods. Drink a variety of clear liquids. Clear liquids should include balanced electrolyte solution such as sports drinks (see Table 1).
- Drink only clear liquids all day the day before your colonoscopy.
- Drink only clear liquids the next day until 2 hours before your colonoscopy.
- Stop drinking all liquids at least 2 hours before your colonoscopy.
You must drink enough clear liquids to keep hydrated.
- Drink FIVE or more 8-ounce cups of clear liquids after the first dose.
- Drink FOUR or more 8-ounce cups of clear liquids after the second dose.
IMPORTANT: You can drink the clear liquids in Table 1.
TABLE 1: List of liquids for the clear-liquid diet
|
IMPORTANT: Do NOT eat or drink the items in Table 2 starting from the day before your colonoscopy.
TABLE 2: List of foods and drinks to avoid while you are on the clear-liquid diet
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SPLIT-DOSE INSTRUCTIONS
DOSE 1
In the evening the day before your colonoscopy (sometime between 5:00 PM to 9:00 PM)
- Place the first bottle on a flat surface. Push down on the cap while twisting to the left (counterclockwise).
- Drink the entire first bottle of CLENPIQ. Drink CLENPIQ right from the bottle.
- Use the cup provided to drink five or more 8-ounce (oz) cups of clear liquids over the next 5 hours.
IMPORTANT: See Table 1 for a list of clear liquids you can drink.
If you have any bloating or upset stomach after drinking CLENPIQ, wait until your stomach feels better before taking your second dose.
DOSE 2
In the morning of your colonoscopy (about 5 hours before your colonoscopy)
- Place the second bottle on a flat surface. Push down on the cap while twisting to the left (counterclockwise).
- Drink the entire second bottle of CLENPIQ. Drink CLENPIQ right from the bottle.
- Use the cup provided to drink four or more 8 ounce (oz) cups of clear liquids. You can continue to drink clear liquids up to 2 hours before the colonoscopy.
Do not eat solid food. Drink only clear liquids. Do not drink only plain water (see Table 1).
IMPORTANT: See Table 1 for a list of clear liquids you can drink.
| Stop drinking clear liquids 2 hours before your colonoscopy, or as advised by your healthcare provider. |
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Ferring Pharmaceuticals Inc. Parsippany, NJ 07054, USA Revised 08/2023 2009010037
Mechanism of Action
Sodium picosulfate is hydrolyzed by colonic bacteria to form an active metabolite: bis-(p-hydroxy-phenyl)-pyridyl-2-methane, BHPM, which acts directly on the colonic mucosa to stimulate colonic peristalsis. Magnesium oxide and citric acid react to create magnesium citrate in solution, which is an osmotic agent that causes water to be retained within the gastrointestinal tract.
